Volume 12 Issue1, 2024

Preservatives used in Pharmaceuticals and impact on Health

Dr.B.V.Ramana Co-author : R.Sai kiran singh

ABSTRACT
For several decades pharmacist have been aware of the need to protect their products against
microbial contamination but it is only during the last one or perhaps two decades the serious
thought of has been applied to the science of preservation. Preservatives are commonly used as
additives in pharmaceutical products, food and cosmetics. Some of the liquid preparations are
susceptible to microbial contamination because of the nature of ingredients present in it. Such
preparations are protected by preservatives which avoids degradation and alternation of the
product. A preservative is a natural or synthetic chemical added to various products which helps
to prevent microbial decomposition. Present article deals with the study of ideal properties,
classification, and mechanism of action, pharmaceuticals applications and its impacts on health
of various preservatives used in pharmaceuticals.

Keywords: preservatives , classification of preservatives, natural preservatives, chemical

classification, applications.

Introduction:

A preservative is a natural or synthetic storage. Preservatives are put in foods to

chemical that is added to products such as
foods, pharmaceuticals, paints, biological
samples, wood, etc. to prevent
decomposition by microbial growth or by
undesirable chemical changes. Preservatives
are substances that are commonly added to
various foods and pharmaceutical products
in order to prolong their shelf life. The
addition of preservatives to such products,
especially to those that have higher water
content, is essential for avoiding alteration
and degradation by microorganisms during
.
inhibit growth of bacteria, yeasts, or molds
that can cause disease. Chemical
preservation cannot totally keep products
from spoiling,[1] but they slow the spoiling
process caused by microorganisms. Frozen
and canned foods often do not contain any
preservatives. Processed Foods are foods
that are put through a process to kill harmful
bacteria that may form in the food. These
processes are supposed to be helpful to the
products, but they can also add harmful
substances

Dr.K.V.Subba Reddy Institute of Technology

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When a natural food is processed it may be
crushed, heated and have chemicals added to
it that may kill all the nutritional value of the
food. Then often additives are added to the
product to put back some vitamins and
nutrients that were lost when the food
product was processed. Preservatives are
added to keep foods fresh and to keep them
from spoiling. The first preservatives to be
used were vinegar, salt and sugar. Now
many of the preservatives are manmade
chemicals. Many of the synthetic food and
cosmetic additives are considered to be safe,
but some of them were found to be
carcinogenic and toxic and it is better to
limit their use.
In general, all synthetic chemical
additives and preservatives may be avoided,
as many of them have not been properly
tested. It happens fairly often that a synthetic
chemical additive that has been judged to be
safe and has been used for year is later
found to be toxic and, in some cases, causes
children and adult to die. All of the chemical
food coloring can be potentially harmful, so
it is better to avoid all food coloring made
from synthetic chemicals. It is important to
understand that the efficacy of antimicrobial
preservatives relies, by definition, on their
ability to kill live cells; in other words, their
toxicity is an unavoidable component of
their reason of being.
A number of natural extracts, plants and
essential oils contain substances that have
the power to effectively kill bacteria, yeast
and fungi; however, in many cases these
substances are or can be toxic for humans,
too. A typical example is citrus or grapefruit
seed extracts: although these have natural
antimicrobial properties, some of their
constituents are thought to be responsible for
life-threatening hormonal imbalances.
Also, citrus seed extracts are not approved
for cosmetic use in Europe and in Japan, and
are therefore not an option in those
countries. In the last few months, a new type
of natural preservative has appeared on the
market. Similar in look, feel and scent to an
essential oil blend, and made by combining
active fractions of essential oils, this new
preservative system seems to have the
potential to address the needs of those skin
care manufacturers who want their products
to be completely natural - yet, being such a
new product, sometime might be required
before its efficacy and possible
contraindications are proven once for all.[2]
Current review focuses on the commonly
used preservatives, their chemistry,
mechanism of action, factors to be
considered while selecting preservatives,
their potential toxicities and impact on the
health caused by their repeated use.
Ideal Properties of Preservatives:
1. It should not be irritant.
2. It should not be toxic.
3. It should be physically and
chemically stable.
4. Preservative should be compatible
with other ingredients used in formulation.
5. It should be acting as good
antimicrobial agent and should exert wide
spectrum of activity.
6. It should act as preservative in small
concentration i.e., it must be potent.
7. It should maintain activity
throughout product manufacturing, shelf life
and usage.[3]

CLASSIFICATION OF
PRESERVATIVES:
Preservatives are classified on variety of
the basis and some of these are as follows:
A. CLASSIFICATION BASED ON
MECHANISM OF ACTION
1. Antioxidants:
The agent which prevents oxidation of
Active pharmaceutical ingredient which
otherwise undergo degradation due to
oxidation as they are sensitive to oxygen.
Eg. Vitamin E, Vitamin C,
Butylatedhydroxyanisole (BHA). Butylated
hydroxytoluene (BHT).
2. Antimicrobial agents:
The agent which active against gram
positive & gram-negative micro-organism
which causes degradation of pharmaceutical
preparation which are active in small
inclusion level.
Eg. Benzoates Sodium benzoate Sorbates
3. Chelating agents:
The agents which form the complex with
pharmaceutical ingredient and prevent the
degradation of pharmaceutical formulation.
Eg. Disodium ethylenediamine tetra acetic
acid (EDTA) Polyphosphates Citric acid
B. CLASSIFICATION BASED ON
SOURCE
1. Natural Preservatives:
These drugs are obtained by natural sources
that are plant, mineral sources, animal etc.
Eg. Neem Oil Salt (sodium chloride) Lemon
Honey
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Volume 12 Issue1, 2024
2. Artificial Preservatives:
These preservatives are man made by
chemical synthesis active against by various
micro-organisms in small concentration.
Eg. Benzoates Sodium benzoate Sorbates,
propionates, nitrites.[4]
MECHANISM OF ACTION:
PRESERVATIVES HOW THEY ACT?
Natural substances such as salt, sugar,
vinegar, and diatomaceous earth are also
used as traditional preservatives. Certain
processes such as freezing, pickling,
smoking and salting can also be used to
preserve food. Another group of
preservatives targets enzymes in fruits and
vegetables that continue to metabolize after
they are cut. For instance, citric and ascorbic
acids from lemon or other citrus juice can
inhibit the action of the enzyme phenolate
which turns surfaces of cut apples and
potatoes brown. Caution must be taken,
however, since FDA standards do not
currently require fruit and vegetable product
labels to accurately reflect the type of
preservative used in the products.[5]
Natural Preservatives:
SUGAR
High levels of sugar can preserve against
spoilage organisms, this may be seen in
jams, preserves, certain sweet pickles and
marmalades. This is also an important factor
in the preservation of boiled sweets and
chocolates etc. Increasingly, it will be
noticed that many products now have to be
kept in the refrigerator or freezer once
opened, because sugar has been replaced by
artificial sweetener which is cheaper and
Page 2

healthier(?) to eat, but which compromises
the self-preservation of the product.[17]
HONEY
Honey in its undiluted form is also a natural
preservative and, indeed, there are many learned
papers citing honey as a viscous barrier to
bacteria and infection.
ALCOHOL
Not all organisms are bad! The production
of alcohol from sugar by yeast is an industry
in its own right. A wine carefully produced
using sterilized equipment and fermented to
13% by volume will just about resist further
infection from external organisms, once the
ferment has completed. It is during the time
of the fermentation process that the
fermenting must is vulnerable to infection.
The naturally produced fermentation grade
alcohol can be concentrated by distillation
and used as a natural preservative in toners,
aftershaves and colognes.
HEAT
Heating, cooking and pasteurization is
another natural form of preservation that
will sterilize products, especially where that
product is designed as a one-shot use
product. For example, a phial or a sachet.
Alternatively, once opened, the product can
be stored in the fridge of freezer to prevent
microbiological degradation.
DESICCATION
Removing water from a product or making it
totally dehydrated will greatly reduce the
possibility of spoilage; however, it must be
recognized that the presence of spore
bearing organisms could become active once
that water is reintroduced.[18]
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Volume 12 Issue1, 2024
ANHYDROUS
In a similar vein, one could make products with
materials that do not contain any traces of water,
i.e. to deliberately design and formulate a totally
anhydrous product. However, creams that can be
finished by the consumer, by introducing water
to the blend of oils, fats and waxes are prone to
the same restrictions as the desiccated products.
SALT
The use of extreme levels of salt as used by
the ancient mariners to preserve their meat is
effective and it very likely that the
preservation of the Egyptian mummies was,
in part, achieved by the 40-day treatment in
natron (a concentrated brine solution that
osmotically drained the tissues of water).
COLD
Placing a product in the cold merely 'stops
the clock' on microbiological growth and
this is perfectly fine, provided the product
was sterile when it was placed in the cold
and/or had sufficient preservative 'mass' to
counter any new organisms subsequently
introduced.
ACID pH
The preservative activity can be boosted by
operating at as low a pH as possible. Natural
acidity could be obtained from one of the
many of the alpha hydroxy acids (AHAs)
which are obtained from citrus species,
where the major components are citric and
malic acids. Incidentally, it is surprising that
expensive sources of natural alpha hydroxy
acids are being contrived, when the
producers of baobab oil are throwing away
large quantities of tartaric acid as a part of
their waste product.[19]
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 Volume 12 Issue1, 2024

CHELATING AGENTS as well as reducing the potential

rancidity.[20]
In addition to formulating at low pH,
chelating agents such as ferulic acid GLYCERINE
extracted from rice bran, could be added to
High levels of vegetable glycerin, up to 15-
enhance the activity of the natural
20%, will also have a preservative effect,
preservative.
similar to that effect obtained by the use of
ANTIOXIDANTS high levels of sugar.
Antioxidants such as natural tocopherol and
ascorbic acid will further aid in preservation,
List of herbs used as preservatives

SOURCE CHEMICAL USES

Aframomum melegueta
(Family: Zingiberaceae)
Alpinia speciosa (Family:
Boraginaceae)
Arnebia tinctoria (Family:
Boraginaceae)
Bixa orellana (Family:
Bixaceae)
CONSTITUENTS
6-Paradol and 6-Shogaol
Pentadecanoic acid, terpinen-
4-ol, sabinene
Two naphthoquinones,
alkannin and
isovalerylalkannin,
delta-tocotrienol
Antimicrobial, active against
Mycobacterium chelonei [M.
chelone], M. intracellular, M.
smegmatis and M. xenopi
Antibacterial, Antifungal,
active against Gram-positive
bacteria (Bacillus subtilis,
Staphylococcus aureus,
Sarcina lutea and
Mycobacterium phlei) and
Gram-negative bacteria
(Escherichia coli and
Pseudomonas aeruginosa), as
well as Candida albicans
Antimicrobial, Antibacterial
and Antifungal, active against
Bacillus subtilis,
Staphylococcus aureus,
Streptomyces pyogenes and
Candida albicans
Antibacterial and Antifungal,
active against Gram-positive
bacteria including Bacillus
subtilis, Staphylococcus
aureus and Streptococcus[21]
faecalis, and exhibited slight

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Buddleja madagascariensis
(Family: Scrophulariaceae)
Capsicum Species (Family:
Solanaceae)
Chamaecyparis obtuse
(Family: Cupressaceae
Cinnamomum zeylanicum
(Family: Lauraceae
Clausena anisata (Family:
Rutaceae)
Cryptolepis sanguinolenta
(Family: Apocynaceae)
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Volume 12 Issue1, 2024
activity against Escherichia
coli, Serratia marcescens,
Candida utilis and Aspergillus
Nige
Mimengoside – A Protozoocidal, Antifungal,
active against Candida strains,
Trichomonas vaginalis and
Leishmania infantum
Capsaicin and Antimicrobial, Antibacterial
dihydrocapsaicin and Antifungal, active against
bacterial species Bacillus
cereus, B. subtilis, Clostridium
sporogenes, Clostridium
tetani,
Thujaplicin Antibiotic, active against
methicillin-resistant
Staphylococcus aureus
(MRSA) Escherichia coli,
Mycobacterium chelonei [M.
chelonae], Pseudomonas
aeruginosa and Candida
albicans.
Cinnamic aldehyde, Antibacterial and Antifungal,
transCinnamaldehyde and active against Aspergillus
Omethoxycinnamaldehyde niger, A. fumigatus, A.
nidulans, A. flavus, Candida
albicans, C. tropicalis
Sabinene, Germacrene D Antibacterial and Antifungal,
active against Flavobacterium
suaveolens, Serratia
marcescens, Alcaligenes
faecalis. Geotrichum
candidum, Aspergillus
parasiticu, P. citrinum and
Alternaria alternata.
Neocryptolepine,2 dimeric Antibacterial and Antifungal,
alkaloids named active against Gram +ve and
biscryptolepine and Gram –ve, Epidermophyton
cryptoquindoline floccosum, Trichophyton[22]
rubrum and Aspergillus
Page 2

Cuminum cyminum (Family:
Apiaceae)
Curcuma Longa (Family:
Zingiberaceae)
(Family: Myrsinaceae)
Desmodium canum (Family:
Fabaceae)
Eriosema tuberosum (Family:
Leguminosae)
Euphorbia tuckeyana
(Family: Euphorbiaceae)
Garcinia kola (Family:
Clusiaceae or Guttiferae)
Glehnia littoralis (Family:
Apiaceae)
Juniperus species (Family:
Cupressaceae)
Hypericum roeperanum
(Family: Hypericaceae)
Isopyrum thalictroides
(Family: Ranunculaceae)
Kigelia pinnata (Family:
Bignoniaceae)
Landolphia owrrience
Department of Pharmaceutics
Cuminaldehyde
Curcumin I, Curcumin II and
Curcumin III
deglucocyclamin and
cyclamen
Isoflavanones, named
desmodianones A, B and C
Eriosemaones A-D, Flemicin
D cucumerinum and C. albicans
24-Methylenecycloartanol and
beta-sitosterol
Polyisoprenyl benzophenone
(kolanone),
hydroxybiflavanonols
1,9-Heptadecadiene-4,6-
diyne3,8,11-triol and
(10E)1,10- heptadecadiene-
4,6-diyne-3,8,9- triol
Alpha-terpineol (88.4%).
5-O-methyl-2-
deprenylrheediaxanthone,
roeperanone
Tertiary alkaloid and
quaternary alkaloid
Naphthoquinones, isopinnatal,
lapachol, phenylpropanoids,
pcoumaric and ferulic acid
Steroids, saponins, tannins
Volume 12 Issue1, 2024
fumigatus
Antibacterial against Gram-
negative bacteria like E. Coli
Antibacterial and Antifungal,
active against Candida
albicans, C. krusei and C.
parasitosis
Cryptococcus neoformans
Antibacterial and Antifungal,
active against B.subtilis, S.
aureus, M. smegmatis, E. coli,
C. albicans and Neurospora
crassa.
Antifungal Cladosporium
Antibacterial and Antifungal,
Active against Gram positive
bacteria and C. albicans.[23]
Antibacterial and Antifungal
active against E. coli, C.
albicans, S.Aureus
Antibacterial and Antifungal,
active against P. aeruginosa, E.
coli, S. aureus, B. subtilis and
C. albicans.
Antibacterial and Antifungal,
active against P. aeruginosa, E.
coli, B. subtilis and C.
albicans
Anti Fungal, active against
Cladosporium cucumerinum
and C. albicans.
Antibacterial and Antifungal
Antibacterial and Antifungal,
active against
Corynebacterium diphtheria,
Pullularia pullularis[24]
Antibacterial, Antifungal and
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 Volume 12 Issue1, 2024

(Family: Apocynaceae) Antimicroabial, active against

Lychnophora salicifolia
(Family: Asteraceae)
Morinda Lucida (Family:
Rubiaceae)
Nelumbo nucifera (Family
:Anelumbonaceae)
Ocimum gratissimum
(Family:Lamiaceae)
Rhazya stricta
(Family:Apocynaceae)
E. coli, B. subtilis and C.
albicans
Caryophyllene derivatives, Antibacterial and Antifungal,
lychnopholic acid and acetyl active against C. tropicalis and
lychnopholic acid, Trichophyton rubrum,E. Coli,
S. Aureus
Anthraquinone, alizarin-1- Antifungal, Antimicrobial,
methyl ethes Aspergillus fumigatus and
Trichophyton mentagrophytes
Kaempferol 3-O-glucoside Antibacterial, Anti-
and luteolin 7-O-glucoside inflammatory, Analgesic and
Anti Fungal activities
Thymol Antibacterial and Antifungal,
active against Salmonella spp.,
Klebsiella pneumoniae,
Proteus vulgaris, A. fumigatus
Strictanol, Anti Bacterial and Anti fungal,
tetrahydrosecamine, active against S.Aureus, E.
akuammidine and rhazimanine Coli, C. Albicans[25]

List of essential oils used as preservatives:

NAME SOURCE CHEMICAL USES

CONSTITUENTS
Birch oil Betula alba Betulin,betulinic acid Antioxidant,
(Family:Betulaceae ) and phytochemicals preservative,
(polyphenols, antibacterial
salicylic acid)
Cardamom Oil Elettaria cardomomum Methyl eugenol, Antioxidant, relieve
(Family:Zingiberaceae) terpenes tooth ache and
digestive disorder
Cinnamon Oil Cinnamomum Eugenol, eugenol Antioxidant, antiviral
zeylanicum (Family: acetate and cinnamic
Lauraceae) acid, cinnamic
aldehyde
Clove Oil Eugenia caryophylla Eugenol, Iso eugenol, Antioxidant, antiviral,
(Family:Myrtaceae) Eugenol acetate anthelmentic, relieves
toothache,
hypoglycemic,

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antiherpes virus
Cumin oil Cuminum cyminum of Pinene, phellandrene, Antioxidant,
(Family:Umbelliferae) Limonene antispasmodic,
carminative, stimulant
and tonic
Eucalyptus Oil Eucalyptus globulus A-pinene, b-pinene, Anti oxidant, a
(Family:Myrtaceae) terpinen-4-ol, cooling and
aromadendrene, deodorizing effect on
epiglobulol, the body,
Fennel Oil Foeniculum vulgare A-pinene, myrcene, Antioxidant,
(Family:Umbelliferae) limonene, 1,8-cineole antiseptic,
antispasmodic,
carminative,
depurative, diuretic
Lemon oil Citrus limonum Ascorbic acid Antioxidant, reducing
(Family:Rutaceae) (vitamin c), blood pressure
aterpinene, linalool,
bbisabolene,
Sage oil Salvia officinalis Chlorgenic acid, Anti oxidant, anti
(Family: Labiatae) flavones, flavonoid biotic, anti fungal,
glycoside,cineole, anti spasmodic,
thujone astringent
Thyme Oil Thymus vulgaris Thymol, a-thujone, Antioxidant,
(Family: Labiatae) apinene, linalool antiseptic, antifungal
Marjoram Oil Origanum marjorana Sabinene, a-terpinene, Anti oxidant,
(Family: Labiatae) linalool, cis-sabinene analgesic,
hydrate, l terpinen-4- antispasmodic,
ol antiseptic, antiviral,
bactericidal
Oregano oil Origanum vulgare Phenolic acids and Antioxidant, antiviral,
(Family: Labiatae) flavonoids antibacterial[26]

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List of Preservatives obtained from Animal Source:

NAME SOURCE USES

Chitosan By Deacetylation of Chitin
present in exoskeleton of
Crustaceans(crabs, shrimps)
and Cell wall of Fungi
Defensin Cystiene rich cationic
compound found in both
vertebrates and invertebrates
and also in plants
Lactoferrin/ Lacto-transferrin Found in Human Milk,
Animal Milk (Cow milk),
Saliva, Tears
Lacto-peroxidase System A Peroxidase enzyme secreted
from mammary, salivary and
other mucosal glands
Lysozyme/ Muramidase Found in Human Milk,
Animal Milk (Cow milk),
Saliva, Tears, neutrophils and
also egg white
Pleurocidin Isolated from the mucus
membranes of winter flounder
(Pseudopleuronectes
americanus)
Lard Purified internal fat obtained
from the abdomen of hog Sus
scrofa Linn.
Antimicrobial against Fungi,
Algae, Bacteria and also as
Natural Biopesticide
Antimicrobial against Fungi,
Algae, enveloped and non-
enveloped viruses
Antibacterial, Antiviral,
Antifungal, Anticancer and
Body immunity[27]
Antibacterial, Antiviral,
Antitumour (Breast Cancer),
Preservative in Cosmetics
Antibacterial (Gram positive
bacteria) Immunity Booster
Antibacterial, Antifungal,
Antiviral and Antiparasitic
Preservative[28]

Allergic hazards of few natural preservatives:

Preservative Toxicity
Cinnamon oil Burning sensation in mouth, chest and
stomach, gastrointestinal problems and
sleeplessness persisting for 5 hrs.
Capsicum species Powerful irritant produces erythematic and
burning without blistering human skin,
produces severe gastritis and diarrhea.[29]
Curcuma Longa Gastric ulceration due to reduction in the
mucin content of gastric juice, fairly nontoxic,

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side effects generally limited to mild stomach

distress.
Cuminum cyminum Gastrointestinal ulceration or bleeding from
stomach
Juniperus species Irritating to eyes and mucous membranes.
Produce hemorrhagic gastritis when ingested.
Systemic effects include weakness and central
nervous depression, with hypothermia and
respiratory failure.
Ocimum gratissimum Mild local irritant. Resembles phenol in its
systemic actions but less toxic, produces
gastric pain, nausea, vomiting, central
hyperactivity, occasionally convulsions, coma,
cardiac & respiratory collapse.[30]

CHEMICAL PRESERVATIVES:
ETHYL ALCOHOL:
Synonyms: Antimicrobial preservative; disinfectant;
skin penetrant; solvent. -Applications in
Ethanolum (96 per centum); ethyl alcohol; ethyl
hydroxide; grain alcohol; methyl carbinol.
Pharmaceutical Formulation or Technology
Ethanol and aqueous ethanol solutions of
Chemical Name: Ethanol various concentrations are widely used in
Empirical Formula and Molecular pharmaceutical formulations and cosmetics.
Weight: C2H6O; 46.07 Although ethanol is primarily used as a
solvent, it is also employed as a disinfectant,
Structural Formula: and in solutions as an antimicrobial
preservative. Topical ethanol solutions are
used in the development of transdermal drug
delivery systems as penetration enhancers.
Ethanol has also been used in the
development of transdermal preparations as
a co-surfactant.

Description:
In the BP 2009, the term ‗ethanol‘ used
without other qualification refers to ethanol
containing 599.5% v/v of C2H6O.The term
Functional Category: ‗alcohol‘, without other qualification, refers
to ethanol 95.1-96.9%v/v. Where other

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strengths are intended, the term ‗alcohol‘ or In acidic conditions, ethanol solutions may
‗ethanol‘ is used, followed by the statement react vigorously with oxidizing materials.
of the strength. In the PhEur 6.0, anhydrous Mixtures with alkali may darken in color
ethanol contains not less than99.5% v/v of owing to a reaction with residual amounts of
C2H6O at 208C. The term ethanol (96%) is aldehyde.[6]
used to describe the material containing
water and 95.1- 96.9% v/v of C2H6O at
ALPHA TOCOPHEROL:
208C.In the USP 32, the term ‗dehydrated
alcohol‘ refers to ethanol 599.5% v/v. The Synonyms:
term ‗alcohol‘ without other qualification
Copherol F1300; 3,4-dihydro-2,5,7,8-
refers to ethanol 94.9-96.0% v/v. In the JP
tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-
XV, ethanol (alcohol) contains 95.1-96.9%
1- benzopyran-6-ol; E307; RRR-a-
v/v (by specific gravity) of C2H6O at
tocopherol; synthetic alpha tocopherol; all-
158C.In the Handbook of Pharmaceutical
rac-a-tocopherol; dla-tocopherol;5,7,8-
Excipients, the term ‗alcohol‘ is used for
trimethyltocol.
either ethanol 95% v/v or ethanol 96% v/v.
Alcohol is a clear, colorless, mobile, and Chemical Name:
volatile liquid with as light, characteristic
(2RS,40RS,80RS)-2,5,7,8- Tetramethyl-2-
odor and burning taste.
(40,80,120-trimethyltridecyl)- 6-chromanol
Typical Properties:
Empirical Formula and Molecular
Antimicrobial activity Ethanol is Weight: C29H50O2; 430.72
bactericidal in aqueous mixtures at
Structural Formula:
concentrations between 60% and 95% v/v;
the optimum concentration is generally
considered to be 70% v/v. antimicrobial
activity is enhanced in the presence of
eidetic acid or edentate salts. Ethanol is
inactivated in the presence of nonionic
surfactants and is ineffective against
bacterial spores. Boiling point 78.158C
Flammability Readily flammable, burning Alpha tocopherol: R1 = R2 = R3 = CH3
with a blue, smokeless flame. Flash point
Beta tocopherol: R1 = R3 = CH3; R2 = H
148C (closed cup). Solubility Miscible with
chloroform, ether, glycerin, and water (with Delta tocopherol: R1 = CH3; R2 = R3 = H
rise of temperature and contraction of
Gamma tocopherol: R1 = R2 = CH3; R3 =
volume). Specific gravity 0.8119-0.8139 at
H
208CNote the above typical properties are
for alcohol (ethanol 95% or96% v/v). Functional Category:

Incompatibilities: Antioxidant; therapeutic agent.

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Applications in Pharmaceutical
Formulation or Technology:
Alpha tocopherol is primarily recognized as
a source of vitamin E, and the commercially
available materials and specifications reflect
this purpose. While alpha tocopherol also
exhibits antioxidant properties, the beta,
delta, and gamma tocopherols are
considered to be more effective as
antioxidants. Alpha-tocopherol is a highly
lipophilic compound, and is an excellent
solvent for many poorly soluble drugs of
wide spread regulatory acceptability,
tocopherols are of value in oil- or fat-based
pharmaceutical products and are normally
used in the concentration range 0.001-0.05%
v/v. There is frequently an optimum
concentration; thus, the autoxidation of
linoleic acid and methylcinnoline is reduced
at low concentrations of alpha tocopherol,
andis accelerated by higher concentrations.
Antioxidant effectiveness can be increased
by the addition of oil-soluble synergists such
as lecithin and ascorbylpalmitate. Alpha
tocopherol may be used as an efficient
plasticizer. It has been used in the
development of deformable liposomes as
topical formulations.
Description:
Alpha tocopherol is a natural product. The
PhEur 6.0 describes alpha-tocopherol as a
clear, colorless or yellowish-brown, viscous,
oily liquid.
Typical Properties:
Boiling point 2358C, Density 0.947-0.951
g/cm3, Flash point 2408C, Ignition point
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3408C Refractive index n D 20 = 1.503-
1.507 Solubility Practically insoluble in
water; freely soluble in acetone, ethanol,
ether, and vegetable oils 11 Stability and
Storage Conditions Tocopherols are
oxidized slowly by atmospheric oxygen and
rapidly by ferric and silver salts. Oxidation
products include tocopheroxide, tocopherol
quinone, and tocopherol hydroquinone.
Safety:
Tocopherols (vitamin E) occur in many food
substances that are consumed as part of the
normal diet. The daily nutritional
requirement has not been clearly defined but
is estimated to be3.0-20.0 mg. Absorption
from the gastrointestinal tract is dependent
upon normal pancreatic function and the
presence of bile. Tocopherols are widely
distributed throughout the body, with some
ingested tocopherol metabolized in the liver;
excretion of metabolites via the urine or bile.
Individuals with vitamin E deficiency are
usually treated by oral administration of
tocopherols, although intramuscular and
intravenous administration may sometimes
be used.[7]
ASCORBIC ACID
Synonyms: Acidumascorbicum; C-97;
cevitamic acid; 2,3-didehydro-L-
threohexono-1,4-lactone; E300; 3- oxo-L-
glucuronolactone, enol form; vitamin C.
Chemical Name: L-(þ)-Ascorbic acid
Empirical Formula and Molecular
Weight: C6H8O6; 176.13
Structural Formula:
Page 3

Functional Category:
Antioxidant; therapeutic agent.
Applications in Pharmaceutical
Formulation or Technology:
Ascorbic acid is used as an antioxidant in
aqueous pharmaceutical formulations at a
concentration of 0.01-0.1% w/v. Ascorbic
acid has been used to adjust the pH of
solutions for injection, and as adjutant for
oral liquids. It is also widely used in foods
as an antioxidant. Ascorbic acid has also
proven useful as a stabilizing agent in mixed
micelles containing tetrazepam.
Description:
Ascorbic acid occurs as a white to light-
yellow colored, non-hygroscopic, odorless,
crystalline powder or colorless crystals with
a sharp, acidic taste. It gradually darkens in
color upon exposure to light.
Stability and Storage Conditions:
In powder form, ascorbic acid is relatively
stable in air. In the absence of oxygen and
other oxidizing agents it is also heat stable.
Ascorbic acid is unstable in solution,
especially alkaline solution, readily
undergoing oxidation on exposure to the air.
The oxidation process is accelerated by light
and heat and is catalyzed by traces of copper
and iron. Ascorbic acid solutions exhibit
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Volume 12 Issue1, 2024
maximum stability at about pH 5.4.
Solutions may be sterilized by filtration. The
bulk material should be stored in a well-
closed nonmetallic container, protected from
light, in a cool, dry place.
Incompatibilities:
Incompatible with alkalis, heavy metal ions,
especially copper andiron, oxidizing
materials, methenamine, phenylephrine
hydrochloride, pyrilamine maleate,
salicylamide, sodium nitrite, sodium
salicylate, theobromine salicylate, and picot
amide. Additionally, ascorbic acid has been
found to interfere with certain colorimetric
assays by reducing the intensity of the color
produced.
Safety:
Ascorbic acid is an essential part of the
human diet, with 40 mg being the
recommended daily dose in the UK and 60
mg in the USA. However, these figures are
controversial, with some advocating doses
of 150 or 250mg daily. Mega doses of 10 g
daily have also been suggested to prevent
illness although such large doses are now
generally considered to be potentially
harmful. The body can absorb about 500 mg
of ascorbic acid daily with any excess
immediately excreted by the kidneys. Large
doses may cause diarrhea or other
gastrointestinal disturbances. Damage to the
teeth has also been reported. However, no
adverse effects have been reported at the
levels employed as an antioxidant in foods,
beverages, and pharmaceuticals.[8]
SODIUM BENZOATE:
Synonyms:
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Benzoic acid sodium salt; benzoate of soda;
E211; natriibenzoas; natriumbenzoicum;
sobenate; sodiibenzoas; sodium benzoic
acid.
Chemical Name: Sodium benzoate
Empirical Formula and Molecular
Weight: C7H5NaO2; 144.11
Structural Formula:
Functional Category:
Antimicrobial preservative; tablet and
capsule lubricant.
Applications in Pharmaceutical
Formulation or Technology:
Sodium benzoate is used primarily as an
antimicrobial preservative in cosmetics,
foods, and pharmaceuticals. It is used in
concentrations of 0.02- 0.5% in oral
medicines, 0.5% in parenteral products, and
0.1-0.5% in cosmetics. The usefulness of
sodium benzoate as a preservative is limited
by its effectiveness over a narrow pH range.
Sodium benzoate is used in preference to
benzoic acid in some circumstances, owing
to its greater solubility. However, in some
applications it may impart an unpleasant
flavor to a product. Sodium benzoate has
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Volume 12 Issue1, 2024
also been used as a tablet lubricant at 2-
5%w/w concentrations. Solutions of sodium
benzoate have also been administered, orally
or intravenously, in order to determine liver
function.
Description:
Sodium benzoate occurs as a white granular
or crystalline, slightly hygroscopic powder.
It is odorless, or with faint odor of benzoin
and has an unpleasant sweet and saline taste.
-Typical Properties Acidity/alkalinity pH =
8.0 (saturated aqueous solution at 258C). It
is relatively inactive above approximately
pH 5. Antimicrobial activity Sodium
benzoate has both bacteriostatic and
antifungal properties attributed to
undissociated benzoic acid; -
Incompatibilities:
Incompatible with quaternary compounds,
gelatin, ferric salts, calcium salts, and salts
of heavy metals, including silver, lead, and
mercury. Preservative activity may be
reduced by interactions with kaolin or
nonionic surfactants. Method of
Manufacture Prepared by the treatment of
benzoic acid with either sodium carbonate or
sodium bicarbonate.
Safety:
Ingested sodium benzoate is conjugated with
glycine in the liver to yield hippuric acid,
which is excreted in the urine. Symptoms of
systemic benzoate toxicity resemble those of
salicylates. Whereas oral administration of
the free-acid form may cause severe gastric
irritation, benzoate salts are well tolerated in
large quantities: e.g., 6g of sodium benzoate
in 200mL of water is administered orally as
a liver function test. Clinical data have
Page 5

indicated that sodium benzoate can produce
nonimmunological contact urticaria and
nonimmunological immediate contact.[9]
SODIUM CHLORIDE:
Synonyms:
Alberger; chlorure de sodium; common salt;
hopper salt; natriichloridum; natural halite;
rock salt; saline; salt; sea salt; table salt.
Chemical Name: Sodium chloride
Empirical Formula and Molecular
Weight: NaCl; 58.44
Structural Formula:
Functional Category:
Tablet and capsule diluent; tonicity agent.
Applications in Pharmaceutical
Formulation or Technology:
Sodium chloride is widely used in a variety
of parenteral and nonparental
pharmaceutical formulations, where the
primary use is to produce isotonic solutions.
Sodium chloride has been used as a
lubricant and diluent in capsules and direct
compression tablet formulations in the past,
although this practice is no longer common.
Sodium chloride has also been used as a
channeling agent and as an osmotic agent in
the cores of controlled release tablets. It has
been used as aporosity modifier in tablet
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Volume 12 Issue1, 2024
coatings, and to control drug release from
microcapsules.
Description:
Sodium chloride occurs as a white
crystalline powder or colorless crystals; it
has a saline taste. The crystal lattice is a
face-centered cubic structure. Solid sodium
chloride contains no water of crystallization
although, below 08C, salt may crystallize as
a dihydrate. -Stability and Storage
Conditions Aqueous sodium chloride
solutions are stable but may cause the
separation of glass particles from certain
types of glass containers. Aqueous solutions
may be sterilized by autoclaving or
filtration. The solid material is stable and
should be stored in a well-closed container
Incompatibilities:
Aqueous sodium chloride solutions are
corrosive to iron. They also react to form
precipitates with silver, lead, and mercury
salts. Strong oxidizing agents liberate
chlorine from acidified solutions of sodium
chloride. The solubility of the antimicrobial
preservative methyl parabenis decreased in
aqueous sodium chloride solutions and the
viscosity of carbomer gels and solutions of
hydroxylethylcellulose or hydroxypropyl
cellulose is reduced by the addition of
sodium chloride.
Safety:
Sodium chloride is the most important salt
in the body for maintaining the osmotic
tension of blood and tissues.[10]
SODIUM SULFITE:
Synonyms:
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 Volume 12 Issue1, 2024

Disodium sulfite; exsiccated sodium sulfite; colored powder that would not conform to
E221; natriisulfas anhydrous; sulfurous acid the pharmacopeial specification.
disodium salt.
Typical Properties:
Chemical Name: Sodium sulfite
Acidity/alkalinity pH = 9 for an aqueous
Empirical Formula and Molecular solution. Density 2.633 g/cm3
Weight: Na2SO3; 126.04 Hygroscopicity Hygroscopic. Solubility
Soluble 1 in 3.2 parts of water; soluble in
Structural Formula:
glycerin; practically insoluble in ethanol
(95%). Stability and Storage Conditions
Sodium sulfite should be stored in a well-
closed container in a cool, dry, place.[11]

METHYL PARABEN:
Synonyms:
Aseptoform M; CoSept M; E218; 4-
hydroxybenzoic acid methyl ester; metagin;
Methyl Chemosept;
Functional Category: Antimicrobial methylisparahydroxybenzoas; methyl
preservative; antioxidant. hydroxybenzoate; Methyl Parasept; Nipagin
M; SolbrolM; Tegosept M; Uniphen P-23.
Applications in Pharmaceutical
Formulation or Technology: Chemical Name: Methyl-4-
hydroxybenzoate
Sodium sulfite is used as an antioxidant in
applications similar to those for sodium Empirical Formula and Molecular
metabisulfite. It is also an effective Weight: C8H8O3; 152.15
antimicrobial preservative, particularly Structural Formula:
against fungi at low pH (0.1% w/v of
sodium sulfite is used). Sodium sulfite is
used in cosmetics, food products, and
pharmaceutical applications such as
parenteral formulations, inhalations, oral
formulations, and topical preparations.

Description:
Sodium sulfite occurs as an odorless white
powder or hexagonal prisms. Note that the
commercially available sodium sulfite is
often presented as a white to tan- or pink-

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Functional Category: Antimicrobial
preservative.
Applications in Pharmaceutical
Formulation or Technology:
Methyl paraben is widely used as an
antimicrobial preservative in cosmetics,
food products, and pharmaceutical
formulations. It may be used either alone or
in combination with other parabens or with
other antimicrobial agents. In cosmetics,
methyl paraben is the most frequently used
antimicrobial preservative. The parabens are
effective over a wide pH range and have
abroad spectrum of antimicrobial activity,
although they are most effective against
yeasts and molds. Antimicrobial activity
increases as the chain length of the alkyl
moiety is increased, but aqueous solubility
decreases; therefore, a mixture of parabens
is frequently used to provide effective
preservation. Preservative efficacy is also
improved by the addition of propylene
glycol (2-5%), or by using parabens in
combination with other antimicrobial agents
such as midurea. Owing to the poor
solubility of the parabens, paraben salts
(particularly the sodium salt) are more
frequently used in formulations. However,
this raises the pH of poorly buffered
formulations. Description:
Methyl paraben occurs as colorless crystals
or a white crystalline powder. It is odorless
or almost odorless and has a slight burning
taste.
Typical Properties:
Antimicrobial activity. Methyl paraben
exhibits antimicrobial activity of pH 4-8.
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Volume 12 Issue1, 2024
Preservative efficacy decreases with
increasing pH owing to the formation of the
phenolate anion. Parabens are more active
against yeasts and molds than against
bacteria. They are also more active against
Gram positive bacteria than against Gram-
negative bacteria. -Stability and Storage
Conditions Aqueous solutions of methyl
paraben at pH 3-6 may be sterilized by
autoclaving at 1208C for 20 minutes,
without decomposition. Aqueous solutions
at pH 3-6 are stable (less than 10%
decomposition) for up to about 4 years at
room temperature, while aqueous solutions
at pH 8 or above are subject to rapid
hydrolysis (10% or more after about 60 days
storage at room temperature).
Incompatibilities:
The antimicrobial activity of methylparaben
and other parabens is considerably reduced
in the presence of nonionic surfactants, such
as polysorbate 80, as a result of
micellization. However, propylene glycol
(10%) has been shown to potentiate the
antimicrobial activity of the parabens in the
presence of nonionic surfactants and
prevents the interaction between methyl
paraben and polysorbate 80.
Incompatibilities with other substances, such
as bentonite, magnesium trisilicate, talc,
tragacanth, sodium alginate, essential oils,
sorbitol, and atropine, have been reported. It
also reacts with various sugars and related
sugar alcohols.
Safety:
Methylparaben and other parabens are
widely used as antimicrobial preservatives
in cosmetics and oral and topical
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 Volume 12 Issue1, 2024

pharmaceutical formulations. Although most effective at pH 4.5 or below. However,

parabens have also been used as[12] at low pH undissociated benzoic acid may
preservatives in injections and ophthalmic produce a slight though discernible taste in
preparations, they are now generally food products. Increasingly, potassium
regarded as being unsuitable for these types benzoate is used as an alternative to sodium
of formulations owing to the irritant benzoate in applications where a low sodium
potential of the parabens. content is desirable. Therapeutically,
potassium benzoate has also been used in
POTASSIUM BENZOATE:
the management of hypokalemia.
Synonyms:
Description:
Benzoate of potash; benzoic acid potassium
Potassium benzoate occurs as a slightly
salt; E212; kaliumbenzoat; potassium salt
hygroscopic, white, odorless or nearly
trihydrate; ProBenz PG.
odorless crystalline powder or granules.
Chemical Name: Aqueous solutions are slightly alkaline and
have a sweetish astringent taste. -Typical
Potassium benzoate
Properties Acidity/alkalinity Aqueous
Empirical Formula and Molecular solutions are slightly alkaline. Melting point
Weight: C7H5KO2; 160.2 >3008C Solubility. Specific gravity 1.5.
Incompatibilities:
Structural Formula:
Potassium benzoate is incompatible with
strong acids and strong oxidizing agents.
Safety:
Potassium benzoate is widely used in food
products and is generally regarded as a
nontoxic and nonirritant material. However,
people with a history of allergies may show
allergic reactions when exposed to
potassium benzoate. Ingestion is inadvisable
Functional Category: for asthmatics. Higher concentrations of
potassium benzoate have been reported to
Antimicrobial preservative; tablet and
cause irritation to mucous membranes. The
capsule lubricant.
WHO acceptable daily intake of total
Applications in Pharmaceutical benzoates including potassium benzoate,
Formulation or Technology: calculated as benzoic acid, has been
estimated at up to 5 mg/kg of body-
Potassium benzoate is predominantly used
weight.[13]
as an antimicrobial preservative in a wide
range of beverages, foods and some APPLICATIONS OF PRESERVATIVES:
pharmaceutical formulations. Preservative
efficacy increases with decreasing pH; it is

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Cosmetic products become easily
contaminated by microbes. Containing
water, oils, peptides, and carbohydrates
cosmetics are a very good medium for
growth of microbes. All these factors
contribute to the fact that cosmetic products
need very good preservation to prevent
microbial growth and spoiling of the
cosmetic product and also infection of the
skin. Preservatives are active ingredients
able to prevent the growth bacteria, fungi, &
viruses. All our preservatives have potent
antimicrobial properties preventing personal
care and makeup products effectively from
spoiling and prolonging substantially the
shelf-life. Some of these agents also have
stabilizing effects able to preserve the
function of various active ingredients
including anti-oxidants (vitamins),
emulsifiers and surfactants. The addition of
such kind of stabilizers makes sure that
creams, lotions and other complex cosmetic
products do not separate or otherwise
disintegrate.[14]
We should not have to compromise with the
quality of our Natural Cosmetics by using
harsh preservatives. Use the right
preservative and adding the right amount to
the Natural Cosmetics without losing the
mild and gentle effects of the Natural
Ingredients present in the Cosmetics. In
order to keep the product safe use of the
right Preservative is needed.[15]
● Many natural substances offer some
antibacterial benefits. Certain essential oils,
like Tea Tree, Thyme and Oregano at high
concentrations can be helpful with some
strains of bacteria. Unfortunately, your
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Volume 12 Issue1, 2024
bathroom, purse, car, or desk drawer is not
an ideal condition natural cosmetic.
● Steam, heat, direct sunlight and other
adverse conditions help encourage bacterial
growth and most "natural preservatives"
can't be used in strong enough
concentrations to fight contamination
without running the risk of skin irritation or
allergic reactions. Others are useful only
against certain strains of contaminants and
for limited amounts of time.
● While Vitamin E, Neem and
Rosemary Oleoresin Extract (ROE) work
wonders at keeping oils from turning rancid,
they don't protect against all forms of gram-
positive, gram-negative bacteria and yeast
which are common in unprotected cosmetic
products.[16]
CONCLUSION:
As we have seen that compared to synthetic
preservatives which are used in preserving
foods, cosmetics, etc., natural preservatives
have fewer side effects. Natural
preservatives, firstly is a traditional method
of preserving food which have been used for
centuries. Natural preservatives have been
economical and better availability, so we can
easily use it.
Natural preservatives not only reduce the
bacterial growth but increases the shelf life
of the ingredient in which it is added. It also
allows them to remain fresh or maintain its
consistency for a long span of time and
causes no toxic effect. Synthetic
preservatives are also good but research has
reported that they cause many health
problems as almost all are carcinogenic in
nature. Hence these must be used
Page 10

considering maximum safety limit for the
preservatives used in pharmaceuticals as
well as cosmetics. Since there are many
effective and potential uses of using natural
preservatives in different ingredients,
satisfactory evidence of its effectiveness and
safety is still lacking.
The beauty brands that have used natural
preservative systems seem to have done so
successfully. However, the challenges going
forward lie in market challenges—lack of
development in the area of new and better
natural preservative systems.
―The performance and cost of these systems
are still not equivalent to the traditional
preservatives, so they are not widely used in
marketed products,‖
Hence, it may better to use natural
preservatives instead of synthetic one, as it
provides us so many good effects.
REFERENCES:
1. Chiori CO, Ghobashy AA; A potentiating
effect of EDTA on the bactericidal activity
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Pharm; 1983; 17; 121-128.
2. European Directorate for the Quality of
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European Pharmacopoeia - State of Work of
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2009; http://www.edqm.eu/site/-614.html
(accessed 3 February 2009). 21(1); 142-143.
3. PB Nielsen, A Müllertzb, T Norlina, HG
Kristensen; The effect of a-tocopherol on the
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Volume 12 Issue1, 2024
in vitro solubilization of lipophilic drugs; Int
J Pharm; 2001; 222(2); 217-224.
4. Constantinides PP et al; Tool emulsions
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5. Hammad MA, Muller BW; Solubility and
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6. Hajratwala BR; Stability of ascorbic acid;
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7. Saleh SI, P. Wehrlé, A. Stamm;
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8. Clarke CD, Armstrong NA; Influence of
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9. Leigh S, J carless, B Burt; Compression
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10. Rees JE, Shotton E; Some observations
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11. Islam MS, Asker AF, Photo protection
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sulfite, PDA J Pharm SciTechnol; 1995;
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12. Nair B, Elmore AR. Final report on the
safety assessment of sodiumsulfite,
potassium sulfite, ammonium sulfite,
sodium bisulfite, ammonium bisulfite,
sodium metabisulfite and potassium
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metabisulfite; Int J Toxicol; 2003; 22(2); 63-
88.
13. Decker RL, Wenninger JA; Frequency
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disclosed to FDA—1987; Cosmet Toilet;
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14. Prickett PS, Murray HL, Mercer NH;
Potentiation of preservatives (parabens) in
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15. FAO/WHO; Toxicological evaluation of
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general principles and of specifications.
Seventeenth report of the joint FAO/WHO
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Health Organ Tech Rep Ser 1974; No. 539.
16. FAO/WHO; Evaluation of certain food
additives and contaminants. Twenty-seventh
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Organ Tech Rep Ser 1983; No.696.
17. R. Trattler: Better Health through
Natural Healing. 1985 Thorson Publishers.
ISBN 0-7225-1382-8.
18. Glenise McLaughlin: Medicinal Plant
review. Aust J Med Herbalism Vol 4 (4)
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19. Allan Onions: Propolis - the bee's knees.
SPC June 1994.
20. Spoerke, D.G.: Herbal Medications.
Woodbridge Press (Santa Barbara,
California 93160). 1990. ISBN No. 0-
88007-181-8.
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Volume 12 Issue1, 2024
21. J.M. Marshall, The Pharmaceutical
Journal. 24th March 1990 p360-362. Aloe
Vera gel: What is the evidence?
22. Soeda, M., Otomo, M., Ome, M., and
Kawashima, K.:(1966) Studies on anti-
bacterial and anti-fungal activity of Cape
Aloe. Nippon Saikingaku Zasshi 21, 609-
614.
23. Lee M. Cera, John P. Heggers, Martin C.
Robson, William J. Hagstrom: The
therapeutic efficacy of Aloe vera Cream
(Dermaide Aloe) in thermal injuries: Two
case reports. Journal of the American
Animal Hospital Association, Sept/Oct
1980, Vol.16, pp.768-772.
24. The International Journal of
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p.31. 25. Bep Oliver: Medicinal Plants in
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26. Balacs, T.: Research Reports. The
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Autumn 1993, vol.5, No.3. Antimicrobial
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May 1991.
28. Deans et al. 1987. Intl. J. of Food
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29. Davidyuk, L.P., Lykov,I.N., Plakhova,
N.S.: Biocidal activity of some plant species
from the collection of the Nikita Botanic
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Garden. Gosudarstvennyi Nikitskii

Botanicheskii Sad, Yalta, Crimea, Ukraine.
Sbornik - Nauchnykh - Trudov -
Gosudarstvennyi - Nikitskii-Botaniches kii-
Sad. 1989, No. 109, 27-42; 6 ref. 1989
30. Kitanaka, S., Takido, M.: Studies on the
constituents in the roots of Cassia obtusifolia
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constituents of the roots and seeds. Nihon
University, Tokyo 101, Japan. Yakugaku-
Zasshi. 1986, 106: 4, 302-306; 12 ref. 1986.

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